In vertebrates, DNA methylation occurs primarily at the 5-position of cytosine (C) in CpG dyads and their genomic methylation patterns are established/maintained by the DNA (C-5)-methyltransferases, or DNMTs. Of the known vertebrate DNMTs, DNMT1 shows a substrates preference for hemi-methylated DNA and maintains the methylation patterns during DNA replication. DNMT3A and DNMT3B show equal C-5 methylation activities toward unmethylated and hemi-methylated DNA in vitro, and they are essential for de novo genomic DNA methylation as well development of the early embryos. The vertebrate DNA methylation system comprising the above three essential DNMTs is indispensable for the establishment of the genomic DNA methylation patterns, globally and locally, and consequently the processes of gene expression, neuroplasticity, differentiation, carcinogenesis, imprinting, X-inactivation and development.
It has remained elusive in literature before 2012 whether there exists enzyme(s) in vertebrates that could actively and directly convert 5-mC on DNA into C.